LSS

lanosterol synthase

Basic information

Region (hg38): 21:46188140-46228824

Links

ENSG00000160285 ∙ NCBI:4047 ∙ OMIM:600909 ∙ HGNC:6708 ∙ Uniprot:P48449 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 44 (Limited), mode of inheritance: AR
• hypotrichosis 14 (Moderate), mode of inheritance: AR
• hypotrichosis simplex (Supportive), mode of inheritance: AD
• total early-onset cataract (Supportive), mode of inheritance: AD
• cataract 44 (Strong), mode of inheritance: AR
• cataract 44 (Strong), mode of inheritance: AR
• alopecia-intellectual disability syndrome 4 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 44; Alopecia-intellectual disability syndrome 4; Hypotrichosis 14	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic; Genitourinary; Neurologic; Ophthalmologic	26200341; 30401459; 30723320
Research investigations suggest that lanosterol may be beneficial for prevention and treatment of Cataract 44

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LSS gene.

• not provided (170 variants)
• Inborn genetic diseases (39 variants)
• Alopecia-intellectual disability syndrome 4 (19 variants)
• Cataract 44 (8 variants)
• Hypotrichosis 14 (6 variants)
• Alopecia-intellectual disability syndrome 4;Hypotrichosis 14;Cataract 44 (1 variants)
• Hypotrichosis 14;Alopecia-intellectual disability syndrome 4;Cataract 44 (1 variants)
• LSS-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LSS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				20	7	27
missense	4	4	59	5	9	81
nonsense	2					2
start loss						0
frameshift	3		1			4
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1	1			3
splice region			7	4	4	15
non coding			1	30	55	86
Total	10	5	62	55	71

Highest pathogenic variant AF is 0.0000131

Variants in LSS

This is a list of pathogenic ClinVar variants found in the LSS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-46191025-TG-T			Benign (Aug 04, 2019)
21-46191071-C-T			Benign (Oct 02, 2019)
21-46191110-G-T		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
21-46191132-G-C		Inborn genetic diseases	Uncertain significance (Nov 20, 2023)
21-46191141-TGGGAGAAGCGGCC-T		Hypotrichosis 14	Uncertain significance (Sep 26, 2022)
21-46191155-G-A			Likely benign (Jul 30, 2023)
21-46191162-C-A		Inborn genetic diseases	Uncertain significance (Jul 08, 2021)
21-46191189-G-T		Alopecia-intellectual disability syndrome 4	Pathogenic (Feb 10, 2022)
21-46191230-G-A			Likely benign (Jun 01, 2022)
21-46191371-T-C			Benign (Jun 28, 2018)
21-46191396-A-G			Benign (Jun 29, 2018)
21-46191444-A-G			Benign (Aug 03, 2018)
21-46191508-C-T			Likely benign (Oct 02, 2019)
21-46191631-G-A			Likely benign (Mar 24, 2019)
21-46191874-G-A			Benign (Apr 14, 2023)
21-46191882-T-G		Inborn genetic diseases	Uncertain significance (Jan 24, 2024)
21-46191885-G-A			Benign (Jan 25, 2024)
21-46191897-T-C		Inborn genetic diseases	Likely benign (Mar 05, 2024)
21-46191904-G-A		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
21-46191926-G-A			Likely benign (Jan 15, 2023)
21-46191958-G-A			Uncertain significance (Sep 12, 2023)
21-46191979-A-C			Benign (Sep 13, 2022)
21-46192252-A-C			Benign (Jun 29, 2018)
21-46194255-T-C			Benign (Jun 28, 2018)
21-46194280-T-G			Benign (Jul 05, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LSS	protein_coding	protein_coding	ENST00000397728	22	40684

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.81e-7	1.00	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.665	424	464	0.913	0.0000294	4703
Missense in Polyphen		145	173.46	0.83591		1819
Synonymous	-0.439	208	200	1.04	0.0000140	1414
Loss of Function	3.77	20	48.2	0.415	0.00000234	499

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000823	0.000784
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000111	0.000109
Finnish	0.000139	0.0000924
European (Non-Finnish)	0.000348	0.000343
Middle Eastern	0.000111	0.000109
South Asian	0.000266	0.000196
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus. Through the production of lanosterol may regulate lens protein aggregation and increase transparency. {ECO:0000269|PubMed:26200341, ECO:0000269|PubMed:7639730}.
• Disease: DISEASE: Cataract 44 (CTRCT44) [MIM:616509]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. {ECO:0000269|PubMed:26200341}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Steroid biosynthesis - Homo sapiens (human);Simvastatin Action Pathway;Pravastatin Action Pathway;Atorvastatin Action Pathway;Hyper-IgD syndrome;Cholesteryl ester storage disease;Lysosomal Acid Lipase Deficiency (Wolman Disease);Alendronate Action Pathway;Rosuvastatin Action Pathway;Lovastatin Action Pathway;Mevalonic aciduria;Wolman disease;Risedronate Action Pathway;Cerivastatin Action Pathway;Pamidronate Action Pathway;Fluvastatin Action Pathway;Smith-Lemli-Opitz Syndrome (SLOS);Chondrodysplasia Punctata II, X Linked Dominant (CDPX2);CHILD Syndrome;Desmosterolosis;Hypercholesterolemia;Steroid Biosynthesis;Zoledronate Action Pathway;Ibandronate Action Pathway;Cholesterol Biosynthesis;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Activation of gene expression by SREBF (SREBP);Metabolism of lipids;Regulation of cholesterol biosynthesis by SREBP (SREBF);Metabolism;cholesterol biosynthesis III (via desmosterol);cholesterol biosynthesis II (via 24,25-dihydrolanosterol);superpathway of cholesterol biosynthesis;Metabolism of steroids;lanosterol biosynthesis;cholesterol biosynthesis I;Steroids metabolism;Cholesterol biosynthesis;Activation of gene expression by SREBF (SREBP) (Consensus)

Recessive Scores

• pRec: 0.386

Intolerance Scores

• loftool: 0.798
• rvis_EVS: 0.54
• rvis_percentile_EVS: 81.1

Haploinsufficiency Scores

• pHI: 0.0996
• hipred: Y
• hipred_score: 0.603
• ghis: 0.465

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lss
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype

Gene ontology

• Biological process: steroid biosynthetic process;cholesterol biosynthetic process;regulation of protein stability;regulation of cholesterol biosynthetic process
• Cellular component: endoplasmic reticulum membrane;lipid droplet;membrane
• Molecular function: lanosterol synthase activity